DOI: 10.1002/ame2.12476
A comprehensive view on the fisetin impact on colorectal cancer in animal models:Focusing on cellular and molecular mechanisms
Mohammad Yasin Zamanian1
Niloofar Taheri2
Montather F.Ramadan3
Yasser Fakri Mustafa4
Safa Alkhayyat5
Klunko Nataliya Sergeevna6
Hashem O.Alsaab7
Ahmed Hjazi8
Farnoosh Molavi Vasei9
Siamak Daneshvar10
1.Department of Physiology,School of Medicine,Hamadan University of Medical Sciences,Hamadan,Iran;Department of Pharmacology and Toxicology,School of Pharmacy,Hamadan University of Medical Sciences,Hamadan,Iran2.School of Medicine,Shahroud University of Medical Sciences,Shahroud,Iran3.College of Dentistry,AI-Ayen University,Nasiriyah,Iraq4.Department of Pharmaceutical Chemistry,College of Pharmacy,University of Mosul,Mosul,Iraq5.College of Pharmacy,The Islamic University,Najaf,Iraq6.Department of Training of Scientific and Scientific-Pedagogical Personnel,Russian New University,Moscow,Russian Federation7.Department of Pharmaceutics and Pharmaceutical Technology,Taif University,Taif,Saudi Arabia8.Department of Medical Laboratory,College of Applied Medical Sciences,Prince Sattam bin Abdulaziz University,Al-Kharj,Saudi Arabia9.Department of Clinical Biochemistry,School of Medicine,Rafsanjan University of Medical Sciences,Rafsanjan,Iran10.Department of Surgery,School of Medicine,Hamadan University of Medical Sciences,Hamadan,Iran
摘要：Flavonoids,including fisetin,have been linked to a reduced risk of colorectal cancer(CRC)and have potential therapeutic applications for the condition.Fisetin,a natural flavonoid found in various fruits and vegetables,has shown promise in managing CRC due to its diverse biological activities.It has been found to influence key cell signaling pathways related to inflammation,angiogenesis,apoptosis,and transcription factors.The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms.It impacts the p53 pathway,leading to increased levels of p53 and decreased levels of murine double minute 2,contributing to apoptosis induction.Fisetin also triggers the release of important components in the apoptotic process,such as second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pl and cytochrome c.Furthermore,fisetin inhibits the cyclooxygenase-2 and wingless-related integration site(Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways,reducing Wnt target gene expression and hindering colony formation.It achieves this by regulating the activities of cyclin-dependent kinase 2 and cyclin-dependent kinase 4,reducing retinoblastoma protein phosphorylation,decreasing cyclin E levels,and increasing p21 levels,ulti-mately influencing E2 promoter binding factor 1 and cell division cycle 2(CDC2)protein levels.Additionally,fisetin exhibits various effects on CRC cells,including inhibiting the phosphorylation of Y-box binding protein 1 and ribosomal S6 kinase,promoting the phosphorylation of extracellular signal-regulated kinase 1/2,and disrupting the repair process of DNA double-strand breaks.Moreover,fisetin serves as an adjunct therapy for the prevention and treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α(PIK3CA)-mutant CRC,resulting in a reduction in phos-phatidylinositol-3 kinase(PI3K)expression,Ak strain transforming phosphorylation,mTOR activity,and downstream target proteins in CRC cells with a PIK3CA mutation.These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.
机标关键词：molecularcellularcancerimpactmodelsviewanimalcolorectal
论文发表日期：2024-10-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：15( 591-605 )
英文信息